Vinegar reduced renal calcium oxalate stones by regulating acetate metabolism in gut microbiota and crystal adhesion in rats

Purpose

Urolithiasis is a common urologic disease. Higher consumption of vinegar was associated with a lower risk of urolithiasis. Recent studies reported that disorder of gut microbiota and injury of the tight junction of renal tubular epithelial cells were associated with the formation of renal calcium oxalate (CaOx) stones. We aimed to explore the mechanism of vinegar reduced renal CaOx stone formation by regulating gut microbiota and the tight junction of renal tubular epithelial cells.

Methods

Thirty Sprague–Dawley rats were randomly allocated to control group, model group and vinegar group. Rats in control group got 2 ml/kg of sterile water by gavage. Model group rats were additionally supplied with drinking water with 1% (v/v) ethylene glycol (EG) every day. Rats in vinegar group had 1% (v/v) EG in drinking water and were gavaged with 2 ml/kg of vinegar (5% acetate) every day.

Results

Vinegar reduced renal CaOx crystals and urinary oxalate. Vinegar increased the relative abundances of Ruminococcus gauvreauii, Ruminococcus torques, Ruminococcus-2, Moryella, Enterococcus, Alistipes, and Parabacteroides in the gut microbiota. Blood acetate increased in vinegar group. The renal tight junction occludin protein decreased in the model group and increased in the vinegar group. Studies in vitro verified that acetate could reverse the decline in occludin expression induced by CaOx crystals and inhibit CaOx crystal adhesion to cells.

Conclusion

Vinegar reduced renal CaOx stones by regulating gut microbiota and increasing blood acetate to restore renal tight junction and reduce CaOx crystal adhesion.

     

Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia-reperfusion injury

Abstract

Background: The present study aimed to investigate whether the inflammatory and antioxidant lycopene has a therapeutic effect against renal ischemia/reperfusion (I/R) injury. Materials and methods: In this study, 24 Wistar-Albino rats, weighing from 200 to 250?g, were divided into four groups. All rats underwent median laparotomy under anesthesia. No procedures were performed in the control group (Group C), whereas 100?mg/kg lycopene was administered by gavage in the lycopene group (Group L). The arteries of both kidneys were clamped for 45?min in the ischemia group (Group I), whereas 100?mg/kg lycopene was administered by gavage 30?min before clamping renal arteries, and ischemia was performed in the treatment group (Group T) rats. For all rats, blood samples and renal tissues were collected at 6?h of reperfusion. Samples were used to examine serum BUN, creatinine, MDA and GSH levels, and the renal tissues were used to examine MDA and GSH levels, and renal histopathologies. Results: The treatment group had statistically significant lower serum MDA levels, histopathological tubular vacuolization, loss of brush border and tubular dilatation (p?<?0.05), whereas serum BUN, creatinine, tissue MDA, and tissue and serum GSH levels were improved in favor of the treatment group, even though it was not statistically significant (p?>?0.05). Conclusion: The present study demonstrated that lycopene, which was administered prior to renal I/R injury, prevented renal damage through biochemical and histopathological parameters.     

Curcumin alleviates ischemia reperfusion-induced acute kidney injury through NMDA receptor antagonism in rats

Objective: The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats.

Methods: Rats were subjected to bilateral renal I/R (40?min I, 24?hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin &; eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60?mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200?mg/kg), and spermidine (20?mg/kg) were administered prior to curcumin treatment in rats followed by AKI.

Results: I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection.

Conclusion: It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.     

Chronic kidney disease as major determinant of the renal risk related to on-pump cardiac surgery: a single-center cohort study

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication and is associated with the poorest outcomes. Therefore, early prediction of CSA-AKI remains a major issue. Severity scores such as the STS score could estimate the risk of AKI preoperatively. The main objective of this study was to evaluate the risk factors of on-pump CSA-AKI and to assess the performance of the STS score in order to predict CSA-AKI.

Patients: We identified 252 patients with on-pump cardiac surgery, and the STS score was defined retrospectively.

Results: AKI occurred in 14.6% (n?=?37/252) of patients and renal replacement therapy was required in 21.6% of AKI (n?=?8/37). CSA-AKI was associated with 35.1% in-hospital mortality (vs. 1.4%) and nearly doubled length of stay (14.5 vs. 8.0 d). The risk of CSA-AKI was mainly determined by preoperative morbidities such as chronic kidney disease, peripheral vascular disease, and severe congestive heart failure. Long cardio-pulmonary bypass time was also a determinant. CSA-AKI?+?patients exhibited higher STS renal risk (5.6% vs. 2.0%; p?2 was as good as the STS score to predict CSA-AKI (AUC 0.75; P 0.26).

Conclusions: On-pump CSA-AKI was observed in nearly 15% of cases and was associated with poorer outcomes. Interestingly, the risk of CSA-AKI could be estimated preoperatively, thanks to the basal renal function, which exhibited an equal performance to the STS score.     

Exogenous normal lymph alleviates lipopolysaccharide-induced acute kidney injury in rats

Abstract

Background: Acute kidney injury (AKI) is a common pathological process which occurs in hemorrhage, intoxication, etc. It has been shown that the lymphatic circulation plays an important regulatory role in the pathogenesis of hemorrhage shock, and that exogenous normal lymph (ENL) has a beneficial effect on multiple organ injuries. In the present study, we investigated the effect of ENL on lipopolysaccharide (LPS)-induced AKI in rats. Methods: The AKI was induced by the jugular vein injection of LPS (iv, 15?mg/kg). After 15?min of LPS injection, saline or ENL without cell components (5?mL/kg) was iv infused at the speed of 0.5?mL per minute. Then, the renal function indices in plasma and renal histomorphology, and the levels of P-selectin, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) and Na⁺-K⁺-ATPase in renal tissue were assessed at 3 or 6?h after LPS injection. Results: LPS induced a severe kidney injury including increased levels of urea, creatinine in plasma, aggrandized activities of ICAM-1 and MPO in renal tissue, and decreased the Na⁺-K⁺-ATPase activity in renal cells. These deleterious effects of LPS were significantly ameliorated by ENL treatment. Conclusion: The present results indicate that ENL protect against LPS-induced AKI, suggesting an alternative therapeutic strategy for treatment of kidney injury accompanied with severe infection or sepsis.     

Acute kidney injury in pregnancy—a single center experience

Abstract

Background: Acute kidney injury (AKI) is a serious complication in pregnancy, resulting in significant maternal morbidity/mortality and fetal loss. Although the incidence of pregnancy-related acute kidney injury (PRAKI) has decreased in developed countries, it is still common in developing nations. Methods: A prospective observational study was done between January 2010 and December 2014 to report the incidence, clinical spectrum, maternal and fetal outcome of AKI in pregnancy. Results: Total number of patients: 130; mean age: 25.4?±?4.73 years. The incidence of AKI in pregnancy was 7.8%. Most of the AKI was noted in postpartum period (68%). Etiology of AKI was sepsis (39%), pre-eclampsia (21%), placental abruption (10%), acute diarrheal disease complicating pregnancy (10%), thrombotic microangiopathy (TMA) (9%), postpartum hemorrhage (2%) and glomerular diseases (9%). Renal biopsy (n?=?46) done in these patients showed renal cortical necrosis (16), TMA (11), acute tubular injury (9), acute tubulointerstitial disease (1) and glomerular disease (9). Live births occurred in 42% of patients with vaginal delivery in 34% cases. Thirty-four patients were managed conservatively, while 96 required dialysis. Complete recovery occurred in 56% and about 36% had persistent renal failure at 3 months. Mortality rate observed was 8%. In univariate analysis, low mean platelet count, higher peak serum creatinine, dialysis dependency at presentation and histopathologically presence of cortical necrosis and TMA predicted the progression to chronic kidney disease. Conclusion: AKI in pregnancy was common in postpartum period and sepsis being the commonest cause.     

EFFECTS OF N-ACETYLCYSTEINE ON MYOGLOBINURIC-ACUTE RENAL FAILURE IN RATS

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2 mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 10 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group 1 before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.     

Impact of acute kidney injury on renal allograft survival

Background: Acute kidney injury (AKI) is one of the major determinants of graft survival in kidney transplantation (KTx). Renal Transplant recipients are more vulnerable to develop AKI than general population. AKI in the transplant recipient differs from community acquired, in terms of risk factors, etiology and outcome. Our aim was to study the incidence, risk factors, etiology, outcome and the impact of AKI on graft survival.

Methods: A retrospective analysis of 219 renal transplant recipients (both live and deceased donor) was done.

Results: AKI was observed in 112 (51.14%) recipients, with mean age of 41.5?±?11.2 years during follow-up of 43.2?±?12.5 months. Etiologies of AKI were infection (47.32%), rejection (26.78%), calcineurin inhibitor (CNI) toxicity (13.39%), and recurrence of native kidney disease (NKD) (4.46%). New Onset Diabetes After Transplant (NODAT) and deceased donor transplant were the significant risk factors for AKI. During follow-up 70.53% (p?=?.004) of AKI recipients progressed to chronic kidney disease (CKD) in contrast to only 11.21% (p?=?.342) of non AKI recipients. Risk factors for CKD were AKI within first year of transplant (HR: 7.32, 95%CI: 4.37–15.32, p?=?.007), multiple episodes of AKI (HR: 6.92, 95%CI: 3.92–9.63, p?=?.008), infection (HR: 3.62, 95%CI: 2.8–5.75, p?=?.03) and rejection (HR: 9.92 95%CI: 5.56–12.36, p?=?.001).

Conclusion: Renal transplant recipients have high risk for AKI and it hampers long-term graft survival.     

Inhibitory effect of an aqueous extract of Radix Paeoniae Alba on calcium oxalate nephrolithiasis in a rat model

Objective: To examine the effect of an aqueous extract of Radix Paeoniae Alba (RPA) on the formation of calcium oxalate (CaOx) stones and the potential mechanism underlying the effect.

Materials and methods: An in vitro assay was used to determine whether the RPA extract prevents the formation of CaOx or promotes CaOx dissolution. We also investigated the efficacy of the extract in vivo as a preventive and therapeutic agent for experimentally induced CaOx nephrolithiasis in rats. Various biochemical, molecular, and histological parameters were assessed in kidney tissue and urine at the end of the in vivo experiment.

Results: Significant dissolution of formed crystals (8.99?±?1.43) and inhibition of crystal formation (2.55?±?0.21) were observed in vitro after treatment with 64?mg/mL of the RPA extract compared with a control treatment (55.10?±?4.98 and 54.57?±?5.84, respectively) (p?Conclusions: RPA is a useful agent that prevents the formation of CaOx kidney stones.     

Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury

Objective: The aim of this work is to investigate the distinctive clinicopathological characteristics of AKI in Chinese IgAN population and possible risk factors for AKI. Methods: We performed a retrospective analysis of 1512 patients with biopsy-proven primary IgAN in the period 2006 through 2011 in The First Affiliated Hospital of Sun Yat-sen University. AKI was defined as 2012 KDIGO (Kidney Diseases: Improving Global Outcomes) criteria, and the patients were divided into AKI group (n?=?145) and non-AKI group (n?=?1367). Results: The prevalence of AKI of the IgAN patients in our center was 9.59% (145/1512). Most AKI patients were older age, male, with higher percentage of smoke, hypertension, hyperlipidemia and preexisting impaired kidney function (Scr?>?133?μmol/L), and higher serum creatinine, proteinuria, uric acid, whilst less onset of macroscopic hematuria as well as lower serum albumin and hemoglobin (p?Conclusions: AKI is commonly seen among IgAN population. The clinicopathological features are much more severe in IgAN patients with AKI. Useful clinicopathological predictors are recognized to improve the identification of IgAN patients who are at high risk for AKI.     

Calcium oxalate crystal deposition in metabolic syndrome model rat kidneys

Objective: Although an epidemiological link between the metabolic syndrome and kidney stone formation has been reported, the mechanism by which metabolic syndrome promotes kidney stone formation has yet to be elucidated. We investigated calcium oxalate (CaOx) kidney stone formation in a rat metabolic syndrome model. Methods: We induced hyperoxaluria in 8‐week‐old male Otsuka Long‐Evans Tokushima fatty (OLETF) rats, and a control strain, Long‐Evans Tokushima Otsuka (LETO) rats, by administering 1.0% ethylene glycol (EG) as their drinking water for 2 weeks. Rats were divided into four groups: LETO‐C (control, n = 7); LETO‐SF (stone forming, n = 8); OLETF‐C (n = 7); and OLETF‐SF (n = 8). Urine and blood samples were collected for biochemistry testing, and the kidneys were harvested for estimation of crystal deposition and determinations of the expression of osteopontin (OPN) and monocyte chemoattractant protein‐1 (MCP‐1). Results: Administration of EG induced hyperoxaluria to the same degree in both strains. The OLETF‐SF group showed a higher grade of renal crystal deposition and significantly higher renal calcium content than the LETO‐SF group. Although the OLETF‐C group excreted significantly higher amounts of uric acid and more acidic urine than the LETO‐C group, similar differences were not observed in rats given EG. Significant upregulation of both OPN and MCP‐1 was seen in the kidneys of hyperoxaluric rats, with higher levels of expression in the OLETF‐SF group than the LETO‐SF group. Conclusions: The present results show for the first time that OLETF rats form more renal CaOx crystal deposits compared with control rats under EG‐induced hyperoxaluric conditions. The model described here should be useful for investigating the mechanisms by which the metabolic syndrome promotes CaOx kidney stone formation.     

Implications of dynamic changes in miR-192 expression in ischemic acute kidney injury

Purpose

Ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) with poor outcomes. While many important functions of microRNAs (miRNAs) have been identified in various diseases, few studies reported miRNAs in acute kidney IRI, especially the dynamic changes in their expression and their implications during disease progression.

Methods

The expression of miR-192, a specific kidney-enriched miRNA, was assessed in both the plasma and kidney of IRI rats at different time points after kidney injury and compared to renal function and kidney histological changes. The results were validated in the plasma of the selected patients with AKI after cardiac surgery compared with those matched patients without AKI. The performance characteristics of miR-192 were summarized using area under the receiver operator characteristic (ROC) curves (AUC-ROC).

Results

MiRNA profiling in plasma led to the identification of 42 differentially expressed miRNAs in the IRI group compared to the sham group. MiR-192 was kidney-enriched and chosen for further validation. Real-time PCR showed that miR-192 levels increased by fourfold in the plasma and decreased by about 40% in the kidney of IRI rats. Plasma miR-192 expression started increasing at 3 h and peaked at 12 h, while kidney miR-192 expression started decreasing at 6 h and remained at a low level for 7 days after reperfusion. Plasma miR-192 level in patients with AKI increased at the time of ICU admission, was stable for 2 h and decreased after 24 h. AUC-ROC was 0.673 (95% CI: 0.540–0.806, p = 0.014).

Conclusions

Plasma miR-192 expression was induced in a time-dependent manner after IRI in rats and patients with AKI after cardiac surgery, comparably to the kidney injury development and recovery process, and may be useful for the detection of AKI.

     

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

Abstract

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24?h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC?=?0.75), lower urine Hepcidin:Creatine ratio at 24?h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24?h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24?h?+?post-operative π-GST (AUC?=?0.86, p?=?0.01), Hepcidin:Cr 24?h?+?NGAL:Cr post-op (0.84, p?=?0.03) and CysC 24?h?+?post-operative π-GST (0.83, p?=?0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver–operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24?h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.     

Incidence,characteristics and prognosis of acute kidney injury in Cameroon: a prospective study at the Douala General Hospital

Objective: There are limited data on AKI in sub-Saharan Africa. We aim to determine the incidence, characteristics and prognosis of AKI in Cameroon.

Patients and methods: A prospective study including all consenting acute admissions in the internal medicine and the ICU of a tertiary referral hospital in Cameroon from January 2015 to June 2016. Serum creatinine assay was done on admission, days 2 and 7 to diagnose AKI. For patients with AKI, serum creatinine was done on discharge, days 30, 60 and 90. AKI was defined according to the modified KDIGO 2012 criteria as an increase or decrease in serum creatinine of 3?mg/l or greater, or an increase of 50% or more from the reference value obtained at admission or the known baseline value. AKI severity was graded using KDIGO2012 criteria. Outcome measures were renal recovery, mortality and causes of death. Renal recovery was complete if serum creatinine between the first 90?days was less than baseline or reference, partial if less than diagnosis but not baseline or reference, no-recovery if creatinine did not decrease or if the patient remained on dialysis.

Results: Of the 2402 patients included, 536 developed AKI giving a global incidence of 22.3% and annual incidence of 15 per 100 patients-years. Of the 536 patients with AKI, 43.3% were at stage 3, 54.7% were males, median age was 56?years. Pre-renal AKI (61.4%) and acute tubular necrosis (28.9%) were the most frequent forms. Main etiologies were sepsis (50.4%) and volume depletion (31.6%). Renal outcome was unknown in 34% of patients. Of the 354 patients with known renal function at 3?months, 84.2% recovered completely, 14.7% partially and 1.1% progressed to CKD. Global mortality rate was 36.9% mainly due to sepsis.

Conclusions: AKI is frequent in our setting, mainly due to sepsis and hypovolemia. It carries a poor prognosis.     

Acute kidney injury following SGLT2 inhibitors among diabetic patients: a pharmacovigilance study

Purpose

The sodium–glucose cotransporter-2 (SGLT2) inhibitors have changed the treatment of type 2 diabetes mellitus. Several studies evaluated SGLT2 inhibitor-related acute kidney injury (AKI), but pharmacoepidemiology studies are needed to compare the adverse events in different SGLT2 inhibitors (SGLT2i).

Methods

We used disproportionality analysis and Bayesian analysis in data mining to screen the AKI cases after initiating different SGLT2i among diabetic patients, based on the FDA’s Adverse Event Reporting System (FAERS) updated to December 2020. We also investigated the onset time and fatality rates of SGLT2i-associated AKI, which was based on preferred terms (PTs) coded for the renal adverse events in the structure of the FARES database.

Results

We identified 2483 cases of AKI following SGLT2i regimens among diabetic patients. Most of them were 45–64 years old (58.46%) and?>?65 years old (28.67%). Canagliflozin generated the largest number of AKI reports (n?=?1650, 66.45%) in our study. Canagliflozin showed the strongest association among SGLT2i, evidenced by the highest reporting odds ratio (ROR?=?3.70, two-sided 95% CI 3.51–3.91), proportional reporting ratio (PRR?=?3.39, χ²?=?2635.06), and empirical Bayes geometric mean (EBGM?=?3.18, one-sided 95% CI 3.04). The median onset time to AKI was 72.0 (interquartile range [IQR] 21.0–266.0) days after SGLT2i initiation. The general hospitalization rate of SGLT2i-associated AKI was 63.50%, and the fatality rate was 1.59%. The deceased patients (62.94?±?10.69 years) were significantly older than the survived ones (57.82?±?11.84 years) (P?=?0.011).

Conclusion

We compared AKI events in the real-world practice of various SGLT2i among diabetic cases from the FAERS database. It is essential to monitor kidney function during the early administration of SGLT2i. Concern should be paid for AKI in patients older than 65 taking SGLT2i.

     

Beneficial Effects of N-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Abstract

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague–Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.     

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats

Abstract

We investigated the changes in the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, the pro-inflammatory cytokines, and the possible effect of melatonin on the modulation of these inflammatory molecules after renal ischemia reperfusion (IR). The study was carried out in the laboratory of Department of Pharmacology. Forty-six male Wistar albino rats were divided into five groups as control (n?=?6), positive control (n?=?4), sham (n?=?12), renal IR (n?=?12), and renal IR melatonin (n?=?12). After 1?h renal pedicle occlusion, the blood samples were taken for the measurement of cytokine levels at second hour of the reperfusion. The rats were sacrificed after 24?h of reperfusion for histopathological evaluation. Melatonin or vehicle was administrated to IR rats. Lipopolysaccharide (LPS) was administered to the positive control group and the blood was taken at fourth hour. Serum TNF-α levels increased significantly in renal IR and LPS groups. Serum IL-6 levels were not different from control except the LPS group. There was no significant correlation between the serum TNF-α levels and the histopathological score after renal IR. Melatonin treatment reversed the increase of serum TNF-α levels and histopathological injury in renal tissue after renal IR. Melatonin may have a protective effect by reducing the serum level of TNF-α in renal IR.     

Etiology,clinical profile and short-term outcome of acute kidney injury in children at a tertiary care pediatric nephrology center in Pakistan

Background: The reported prevalence rates and etiologies of acute kidney injury (AKI) are quite variable in different regions of the world. The current study was planned to determine the etiology, clinical profile, and short-term outcome of pediatric AKI at our hospital.

Methods: A prospective, observational study was carried out from April 2014 to March 2015. All pediatric patients (1 month to?≤15 years) diagnosed as AKI using modified pRIFLE criteria were studied and followed for 3 months to document short-term outcome.

Results: AKI was diagnosed in 116 children. The mean age was 7.5?±?4.4 years and males were predominant (60.3%). At presentation, 83.6% had oliguria/anuria, 37.1% hypertension and 17.2% severe anemia. Etiology included primary renal (74/116; 63.8%), postrenal (28/116; 24.1%) and prerenal (11/116; 9.5%) causes. Postinfectious glomerulonephritis (PIGN) and crescentic glomerulonephritis in primary renal, obstructive urolithiasis in postrenal and sepsis in prerenal, were the most common etiologies. At presentation, 89/116 (76.7%) patients were in pRIFLE Failure category. Regarding outcome, 68 (58.6%) patients recovered, six (5.2%) died, 18 (15.5%) developed chronic kidney disease (CKD) and 22 (19%) end-stage renal disease (ESRD). Comparison of recovered and unrecovered AKI showed that characteristics such as hypertension, severe anemia, edema, volume overload, requirement of mechanical ventilation, initiation of dialysis and need of >5 sessions of dialysis had statistically significant (p?<0.05) association with nonrecovery.

Conclusion: Glomerulonephritides (PIGN and crescentic) and obstructive urolithiasis are major causes of pediatric AKI at our center. A fairly high percentage of cases recovered and these mainly comprised of PIGN and obstructive urolithiasis.     

The expression of response gene to complement 32 on renal ischemia reperfusion injury in rat

To investigate the expression of response gene to complement 32 (RGC32) in rat with acute kidney injury (AKI) and to explore the role of RGC32 in renal injury and repair induced by ischemia reperfusion. Rats were randomly divided into two groups, including sham operation group (n?=?48) and acute ischemia reperfusion injury (IRI) group (n?=?48). Rats were sacrificed following reperfusion 2?h, 6?h, 24?h, 48?h, 72?h, 1 week (w), 2 w, and 4 w. The distribution and expression of RGC32 in renal tissue were observed by means of immunohistochemistry. The mean density of the images detected by Image-Pro Plus 6 was designated as the representative RGC32 expression levels. Meanwhile, RGC32 mRNA expression was measured by qPCR. RGC32 mainly expressed in cytoplasm of proximal tubular epithelial cells. However, RGC32 did not express in renal interstitium and vessels. The expression levels of RGC32 measured by immunohistochemistry at different reperfusion time were 0.0168?±?0.0029, 0.0156?±?0.0021, 0.0065?±?0.0013, 0.0075?±?0.0013, 0.0096?±?0.0014, 0.0132?±?0.0016, 0.0169?±?0.0014, 0.0179?±?0.0022, respectively. Compared with the sham group, the level of RGC32 expression in IRI group was significant lower at 24?h, 48?h, 72?h after IRI (p?in vitro experiments show the expression of α-SMA and extracellular matrix expression increased signification when the RGC32 was silenced. Our data showed that the RGC32 expression in AKI rat decreased significantly reduces with different reperfusion time and performs a time-dependent manner. RGC32 may play an important role in the pathogenesis of AKI following IRI and repair in rat.